All about Vitamin A

Vitamin A, Retinoids, Retinol, Retinoic Acid. It could be confusing which one to pick without some background information. That is what you will find in this blog. 

There is literally no other ingredient that addresses as many skin concerns like these vitamin A derivates. We are talking about unclogging pores and clearing up acne, reversing photoaging, increasing collagen production and skin elasticity, help with post inflammatory hyperpigmentation such as melasma, speeding up skin turnover rate to minimize fine lines and wrinkles and essentially leave you with the best version of your skin. Trust me, your skin will thank you.

Retinoids are natural and synthetic vitamin A derivatives which is one of the body's key nutrients for boosting cell turnover. Retinoids can be administered both topically and systemically. For the purpose of this video, we will only be talking about topical application of retinoids. 

According to literatures, Retinoids were first used in dermatology in 1943 by Straumfjord for acne vulgaris.

But it is the FDA’s approval of Tretinoin, under the brand name Retin-A for acne in 1971 that’s placed retinoids front and center in the dermatology and cosmeceuticals space. Since that time, retinoids have been utilized in the management and treatment of various skin conditions.

Thanks to serendipity, researchers later discovered the different generations of retinoids did more than clearing up acne. So, they joined the glorious world of anti-wrinkle and anti-aging. And they still maintain the gold standard status for these reasons.

RAR-α, RAR-β, and RAR-γ

When a topical formulation containing retinoids is applied on the skin, the retinoids

diffuse through the stratum corneum to the keratinocytes and to a small extent into the dermis. As lipophilic molecules, retinoids are taken up by the cells and reach the nucleus where they bind to retinoic acid receptors which has 3 isoforms and retinoid X receptors.

They are keratolytics which means they help bring newer skins to the surface faster. They also reduce skin pigmentation by about 60% and contribute to a proper distribution of melanin in the skin. Topically applied retinoids also influence the function of melanocytes, providing regular arrangement of melanin in the epidermis.

They block transport of melanin to epidermal cells and diminish the activity of stimulated melanocytes.

Retinoids’ chemical structure contains several conjugated double bonds that enable them to trap free radicals and absorb UV radiations from the sun, which means they can protect cellular targets such as DNA, lipid membranes, or proteins by preventing direct photochemical damage or UV-induced oxidative stress. This is what makes them good candidates to treat and prevent photoaging. 

Ok, they sound great. Where do you begin, right?

Well first you want to start with over the counter retinoids. Retinoic acid is the bioactive molecule that the body can take as is and use. But only prescription strength retinoids such as Retin-A come in this bioavailable form. The rest of the derivatives need one, two or three enzymatic reactions to be converted to retinoic acid. For my pharmacist friends, Think of retinoids other than tretinoin as “prodrugs”. This makes the over the counter options milder and a good place to start. Retinoids generally have an irritant side effect that is well managed by starting small and making your way up gradually. 

You can easily get your hands on Retinyl palmitate or acetate, retinaldehyde and most retinols which are precursors of retinoic acid over-the-counter. 

Retinyl Esters (Retinyl palmitate, propionate or acetate) are the weakest. Retinol is next followed by Retinaldehyde. To put things into perspective, Tretinoin which is the prescription retinoic acid is 20x more powerful than retinol. So, you don’t need to bring the big gun unless you need it.

Retinaldehyde: Oxidizes to retinoic acid

Retinol: Retinaldehyde-retinoic acid

Esters: two step before the body can use them first converts to retinol-retinaldehdye and then to retinoic acid 

As for prescription retinoids, you find Tretinoin (Brand name Retin-A), adapalene (Brand name Differin), and tazarotene (Brand name Tazorac) which have been available for decades. The latest addition to this list is trifarotene 0.005% cream (by the Brand name Aklief) which was approved by the FDA last year- in 2019.

Some prescription retinoids are also available otc at a lower strength. For example, Adapalene 0.1% gel has been available over the counter since 2016 for treatment of acne in patients ≥12 years old versus the 0.3% strength rx version.

Things to keep in mind

Although retinoids are uh-mazing, you want to avoid using them during pregnancy or while breastfeeding. There are studies that showed the risk of birth defects in offspring.

If you are on benzoyl peroxide for acne, make sure you apply benzoyl peroxide and retinoids separately. If you think what the heck, they are going to mix on the skin so let me mix them already, you will be wasting your retinoids. Because, retinoids become degraded by the oxidizing activity of benzoyl peroxide. They are not necessarily incompatible, but you want to apply those two separately if you want them to give you that synergism. 

According to one study, check description below, people of color are better off with third-generation retinoids: adapalene and tazarotene when going after post inflammatory hyperpigmentation due to acne. Tretinoin, which is a first-generation retinoid might not be your first choice. 

The most common side effect of retinoids is irritation, redness, dryness and flaking. You can minimize this by giving your skin a chance to acclimatize to them.

• Start with a milder version retinoid. Retinol is widely available from many brands. You can start there. Once I lay some foundation, I will get into the fun part and share with you products I like.
• Start twice a week or so
• Apply a small “pea-sized” amount to the entire face
• Wait until your face is dry before applying because damp skin absorbs much more than dry skin
• If you are still experiencing irritation, don’t give up yet. Apply a layer of moisturizer prior to applying the retinoid to help your skin acclimatize
• As you tolerate it and if you don’t have irritation, titrate upwards
• Sunlight deactivates retinoid compounds so use them at night.
• Make sure you apply broad spectrum sunscreen so you preserve the hard work the retinoids are giving your skin
• Commit to using them because the results do take time to show results. The mechanism of action by which retinoids work is complicated and effective but they take time to show change. Especially if you’re trying to minimize fine lines and wrinkles. So, be patient.
• Moisturize, moisturize and moisturize. This not only helps hydrate your skin and also minimizes the irritation.
• If you can tolerate it, don’t forget the neck and chest area as well. I know I can because I dilute my retinol with serums.
• Give it at least 3-6 months to see actual change. Increase the frequency as you tolerate
• If you feel you need to up the game, go for retinaldehyde. If that’s not cutting it for you, there’s always tretinoin. Undoutedly, the most studied retinoid out there and your big gun in this case.

 

REFERENCES

Color Atlas of Chemical Peels. Germany, Springer, 2012.

International Textbook of Aesthetic Surgery. Belgium, Springer Berlin Heidelberg, 2016. 

Katoulis, Alexander C.. Hyperpigmentation. United Kingdom, CRC Press, 2017.

Melasma and Vitiligo in Brown Skin. India, Springer India, 2017.

Pigmentary Skin Disorders. Germany, Springer International Publishing, 2018. 

Riahi, R.R., Bush, A.E. & Cohen, P.R. 2016, "Topical Retinoids: Therapeutic Mechanisms in the Treatment of Photodamaged Skin", American Journal of Clinical Dermatology, vol. 17, no. 3, pp. 265-276.

Robbins, Clarence R.. Chemical and Physical Behavior of Human Hair. Germany, Springer, 2012. 

Sorg, O., Kuenzli, S., Kaya, G. & Saurat, J. 2005, "Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging", Journal of cosmetic dermatology, vol. 4, no. 4, pp. 237-244.

Trifarotene (Aklief)—A New Topical Retinoid for Acne. JAMA. 2020;323(13):1310–1311. doi:10.1001/jama.2019.22507